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Abstract Background Hyperlipidemia is a vital etiology of acute pancreatitis (AP), 12 to 20% of which have a history of hyperlipidemia. Multiple organ failure is the major cause of the high mortality rate of AP. Liver injury has been discovered in 80% of AP patients. The relationship and role of IRF9 and SIRT1 have not been presented in AP and hyperlipidemia AP (HLAP) with liver injury. This investigation was designed to explore the function and relationship of IRF9 and SIRT1. Methods HLAP model in vivo was performed by feeding high-fat forage and induced by peritoneal injection with 20% L-arginine. The severity of pancreas and liver tissues was assessed. Cell apoptosis in the liver was determined by the TUNEL experiment. IRF9, SIRT1, p53, and acetylated p53 (Ac-p53) expression levels in liver tissues were detected by qRT-PCR and Western blot. The association of IRF9 expression with SIRT1 levels was evaluated. The relevance of triglyceride level to tissue damage was analyzed. Results Our observation exhibited more distinct liver damage, a large number of hepatic cell apoptosis, marked raised IRF9, Ac-p53, and sharply dropped SIRT1 in the AP and HLAP groups. Compared with other groups, HLAP showed the most significant changes in liver injury, hepatic cell apoptosis, protein, and mRNA levels. The declined expression of SIRT1 was correlated with the elevated expression of IRF9. The damage of the pancreas and liver exacerbated with the increase in triglyceride levels. Conclusion Elevated IRF9 in pancreatitis with liver injury raised cell apoptosis and tissue damage by decreasing SIRT1 expression.

The change of water content, mildew of Liupao tea at 35 ℃, 30 ℃, 25 ℃ and humidity of 90%, 80% and 70% were studied. The influence of temperature and humidity on water content and mildew of Liupao tea was analyzed, and the temperature and humidity conditions of Liupao tea were determined. The parameters of spore counting method applied to Liupao tea were optimized and the feasibility of spore counting method in predicting the mildew degree of Liupao tea was evaluated. The results showed that temperature below 25 ℃ and humidity below 70% were the best storage conditions for Liupao tea to prevent mildew. The increase level of spore number and the degree of mildew were synchronized. This method was feasible for rapid assessment of mildew of Liupao tea, and the critical value of the number of spores with mildew was preliminarily determined to be 30.00×107 ·g–1. The results of this study could provide a theoretical basis for the safe storage conditions of Liupao tea, and a new method for rapid assessment of its mildew degree.

Abstract Waterlogging stress is one of the major abiotic stresses affecting the productivity and quality of many crops worldwide. However, the mechanisms of waterlogging tolerance are still elusive in barley. In this study, we identify key differentially expressed genes (DEGs) and differential metabolites (DM) that mediate distinct waterlogging tolerance strategies in leaf and root of two barley varieties with contrasting waterlogging tolerance under different waterlogging treatments. Transcriptome profiling revealed that the response of roots was more distinct than that of leaves in both varieties, in which the number of downregulated genes in roots was 7.41-fold higher than that in leaves of waterlogging sensitive variety after 72 h of waterlogging stress. We also found the number of waterlogging stress-induced upregulated DEGs in the waterlogging tolerant variety was higher than that of the waterlogging sensitive variety in both leaves and roots in 1 h and 72 h treatment. This suggested the waterlogging tolerant variety may respond more quickly to waterlogging stress. Meanwhile, phenylpropanoid biosynthesis pathway was identified to play critical roles in waterlogging tolerant variety by improving cell wall biogenesis and peroxidase activity through DEGs such as Peroxidase (PERs) and Cinnamoyl-CoA reductases (CCRs) to improve resistance to waterlogging. Based on metabolomic and transcriptomic analysis, we found the waterlogging tolerant variety can better alleviate the energy deficiency via higher sugar content, reduced lactate accumulation, and improved ethanol fermentation activity compared to the waterlogging sensitive variety. In summary, our results provide waterlogging tolerance strategies in barley to guide the development of elite genetic resources towards waterlogging-tolerant crop varieties.

Bladder cancer (BC) is the most common malignancy of the urinary system and often recurs after tumor removal and/or is resistant to chemotherapy. In cancer cells, the activity of the signaling pathway changes significantly, affecting a wide range of cell activities from growth and proliferation to apoptosis, invasion and metastasis. Nrf2 is a transcription factor that plays an important role in cellular defense responses to a variety of cellular stresses. There is increasing evidence that Nrf2 acts as a tumor driver and that it is involved in the maintenance of malignant cell phenotypes. Abnormal expression of Nrf2 has been found to be common in a variety of tumors, including bladder cancer. Over-activation of Nrf2 can lead to DNA damage and the development of bladder cancer, and is also associated with various pathological phenomena of bladder cancer, such as metastasis, angiogenesis, and reduced toxicity and efficacy of therapeutic anticancer drugs to provide cell protection for cancer cells. However, the above process can be effectively inhibited or reversed by inhibiting Nrf2. Therefore, Nrf2 signaling may be a potential targeting pathway for bladder cancer. In this review, we will characterize this signaling pathway and summarize the effects of Nrf2 and crosstalk with other signaling pathways on bladder cancer progression. The focus will be on the impact of Nrf2 activation on bladder cancer progression and current therapeutic strategies aimed at blocking the effects of Nrf2. To better determine how to promote new chemotherapy agents, develop new therapeutic agents, and potential therapeutic targets.

Acute respiratory distress syndrome (ARDS) is independently associated with a poor prognosis in patients with sepsis. Macrophage M1 polarization plays an instrumental role in this process. Therefore, the exploration of key molecules affecting acute lung injury and macrophage M1 polarization may provide therapeutic targets for the treatment of septic ARDS. Here, we identified that elevated levels of Ankyrin repeat domain-containing protein 22 (ANKRD22) were associated with poor prognosis and more pronounced M1 macrophage polarization in septic patients by analyzing high-throughput data. ANKRD22 expression was also significantly upregulated in the alveolar lavage fluid, peripheral blood, and lung tissue of septic ARDS model mice. Knockdown of ANKRD22 significantly attenuated acute lung injury in mice with sepsis-induced ARDS and reduced the M1 polarization of lung macrophages. Furthermore, deletion of ANKRD22 in macrophages inhibited M1 macrophage polarization and reduced levels of phosphorylated IRF3 and intracellular interferon regulatory factor 3 (IRF3) expression, while re-expression of ANKRD22 reversed these changes. Further experiments revealed that ANKRD22 promotes IRF3 activation by binding to mitochondrial antiviral-signaling protein (MAVS). In conclusion, these findings suggest that ANKRD22 promotes the M1 polarization of lung macrophages and exacerbates sepsis-induced ARDS.

The aim of this study was to investigate the potential mechanism through which Yishen Tongluo decoction (YSTL) repairs DNA damage caused by benzo(a)pyrene diol epoxide (BPDE) in mouse spermatocytes (GC-2). The GC-2 cells were divided randomly into the control group, BPDE group, and low-, medium-, and high-dose YSTL groups of YSTL decoction. A comet assay was used to detect the DNA fragment index (DFI) of cells in each group. Based on the DFI results, whole transcriptome sequencing was conducted, followed by trend analysis, gene ontology (GO) enrichment analysis, kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and ceRNA network analysis. Compared with the control group, the BPDE group reported a significant increase in the DNA fragmentation index (DFI) ( p < .05). Compared with the BPDE group, the low-, high- and medium-dose YSTL groups had a significantly reduced DFI ( p < .05). Whole-transcriptome sequencing revealed seven differentially expressed circRNAs, 203 differentially expressed miRNAs, and 3,662 differentially expressed mRNAs between the control group and the BPDE group. There was a total of 12 differentially expressed circRNAs, 204 miRNAs, and 2150 mRNAs between the BPDE group and the traditional Chinese medicine group. The pathways involved include DNA repair pathway, nucleotide excision repair pathway, base excision repair pathway, etc. The ceRNA network reported that Hmga2 was the core protein involved, novel_cir_000117 and mmu-miR-466c-3p were located upstream of Hmga2, and they were regulatory factors associated with Hmga2. Finally, we conclude that YSTL decoction may repair sperm DNA damage caused by BPDE through the novel_cir_000117-mmu-miR-466c-3p-Hmga2 pathway.

Brominated flame retardants (BFRs), categorized as persistent organic pollutants (POPs) are difficult to degrade, exhibiting reproductive toxicity and carcinogenicity. Exposure to dust and soil particles containing BFRs may cause various health problems. The research aimed to assess the concentrations, potential origins, and health risks associated with polybrominated diphenyl ethers (PBDEs) and novel BFRs (NBFRs) in road dust and green belt soil in Harbin. The study revealed that ΣPBDE concentrations ranging from 0.15 to 193.75 ng/g (median: 48.01 ng/g) in road dust and 8.07 to 195.33 ng/g (median: 38.19 ng/g) in green belt soil. Notably, TBBPA contributed the most to the ΣPBDEs concentrations. And the concentrations of ΣNBFRs ranged from 2.34 to 130.53 ng/g (median: 18.48 ng/g) in road dust and 2.50 to 46.70 ng/g (median: 7.85 ng/g) in green belt soil. And tetrabromobisphenol A (TBBPA) was the most dominant compound in both samples. Highways exhibited lower ΣPBDE concentrations in dust samples but higher ΣNBFR concentrations in soil samples compared to other roads. Moreover, most of the BFRs had a positive correlation with each other, suggesting that they may have similar sources. Principal component analysis (PCA) suggested BFRs sources in road dust may come from wire, paint, building materials or commercial products, likewise, BFRs in green belt soil may come from household or industrial products. Health risk assessment indicated that BFRs in both types of samples in Harbin had no non-carcinogenic risk to residents. These findings provide valuable insights into understanding BFR pollution characteristics, identifying specific sources, and recognizing health hazards in dust and soil samples on roads from Harbin.

Abstract Background Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. Methods We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. Main outcome: Comparison of serum inflammatory cytokines concentration at each time point. Results Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P

Abstract This study aims to evaluate the therapeutic efficacy of a novel double-sheath negative-pressure minimally invasive percutaneous nephrolithotomy (D-mPCNL) compared to conventional minimally invasive percutaneous nephrolithotomy (C-mPCNL) for large kidney stones. A total of 132 patients diagnosed with large kidney stones in our hospital were included in the study. Among them, sixty-eight patients underwent D-mPCNL, while sixty-four underwent C-mPCNL. Parameters such as operative duration, stone-free rate, incidence of postoperative complications, and the need for auxiliary procedures were evaluated between the two groups. Compared to the C-mPCNL group, the D-mPCNL group demonstrated a significantly shorter operative time (41.97 ± 8.24 min vs. 52.30 ± 13.72 min; P 0.05). D-mPCNL is a novel surgical method that is safe and effective, reducing operative time, improving stone-free efficiency, and decreasing postoperative complications.

AbstractContext Plastics can break down into millions of microplastic (MPs, < 5 mm) particles in the soil and ocean. These MPs can then affect the function of the reproductive system. There is currently no effective solution to this problem aside from traditional Chinese medicine. We have previously used Yishen Tongluo formula (YSTL) to treat sperm DNA damage caused by some toxic substances.Objective To investigate the mechanism underlying the repair of mouse sperm DNA fragmentation caused by polystyrene microplastics by YSTL.Materials and methods An animal model of polystyrene microplastic (PS-MP)-induced sperm DNA damage was replicated by gavage of SPF ICR (CD1) mice PS-MPs at 1 mg/d and treated with YSTL at 11.89, 23.78 and 47.56 g/kg, respectively, for 60 days. The Sperm DNA fragmentation index (DFI) of each group was detected and compared. The target genes of YSTL identified by transcriptomic and proteomic analyses were validated by qRT-PCR and western blotting.Results The DFI of the PS group (20.66%) was significantly higher than that of the control group (4.23%). The medium and high doses of the YSTL group (12.8% and 11.31%) exhibited a significant repairing effect. The most enriched pathway was PI3K/Akt. TBL1X, SPARC, hnRNP0, Map7D1, Eps8 and Mrpl27 were screened and SPARC was validated.Discussion and conclusions The precise mechanism by which YSTL inhibits PD-MPs DNA damage may be associated with the PI3K/Akt pathway and SPARC. It provides a new direction for using traditional Chinese medicine to prevent and repair reproductive system injury caused by MPs.

Abstract Arsenic (As) is a cancerogenic metalloid ubiquitously distributed in the environment, which can be easily accumulated in food crops like rice. Jasmonic acid (JA) and its derivatives play critical roles in plant growth and stress response. However, the role of endogenous JA in As accumulation and detoxification is still poorly understood. In this study, we found that JA biosynthesis enzymes Allene Oxide Synthases, OsAOS1 and OsAOS2, regulate As accumulation and As tolerance in rice. Evolutionary bioinformatic analysis indicated that AOS1 and AOS2 have evolved from streptophyte algae (e.g. the basal lineage Klebsormidium flaccidum) – sister clade of land plants. Compared to other two AOSs, OsAOS1 and OsAOS2 were highly expressed in all examined rice tissues and their transcripts were highly induced by As in root and shoot. Loss-of-function of OsAOS1 (osaos1–1) showed elevated As concentration in grains, which was likely attributed to the increased As translocation from root to shoot when the plants were subjected to arsenate [As(V)] but not arsenite [As (III)]. However, the mutation of OsAOS2 (osaos2–1) showed no such effect. Moreover, osaos1–1 and osaos2–1 increased the sensitivity of rice plants to both As(V) and As(III). Disrupted expression of genes involved in As accumulation and detoxification, such as OsPT4, OsNIP3;2, and OsOASTL-A1, was observed in both osaos1–1 and osaos2–1 mutant lines. In addition, a As(V)-induced significant decrease in Reactive Oxygen Species (ROS) production was observed in the root of osaos1–1 but not in osaos2–1. Taken together, our results indicate OsAOS1 modulates both As allocation and detoxification, which could be partially attributed to the altered gene expression profiling and ROS homeostasis in rice while OsAOS2 is important for As tolerance.

Sex determination in plants gives rise to unisexual flowers. A better understanding of the regulatory mechanism underlying the production of unisexual flowers will help to clarify the process of sex determination in plants and allow researchers and farmers to harness heterosis. Androecious cucumber (Cucumis sativus L.) plants can be used as the male parent when planted alongside a gynoecious line to produce heterozygous seeds, thus reducing the cost of seed production. The isolation and characterization of additional androecious genotypes in varied backgrounds will increase the pool of available germplasm for breeding. Here, we discovered an androecious mutant in a previously generated ethyl methanesulfonate (EMS)-mutagenized library of the cucumber inbred line ‘406’. Genetic analysis, whole-genome resequencing, and molecular marker-assisted verification demonstrated that a nonsynonymous mutation in the ethylene biosynthetic gene 1-AMINOCYCLOPROPANE-1-CARBOXYLATE SYNTHASE 11 (ACS11) conferred androecy. The mutation caused an amino acid change from serine (Ser) to phenylalanine (Phe) at position 301 (S301F). In vitro enzyme activity assays revealed that this S301F mutation leads to a complete loss of enzymatic activity. This study provides a new germplasm for use in cucumber breeding as the androecious male parent, and it offers new insights into the catalytic mechanism of ACS enzymes.

Fluctuations in outer space's temperature would affect the spacecraft's regular operation. This paper aims to study the temperature influences of the aluminum honeycomb buffer in the tether-net launcher. Firstly, a buffer structure was designed to attenuate the pyroshock generated by the pyrotechnic device. Secondly, the mechanical properties of aluminum honeycomb at different temperatures were obtained through quasi-static compression experiments. Then, the internal ballistic responses of the launcher were gained by the closed bomb tests and the equivalent classical interior ballistic model. Finally, the recoil performance of the launcher with aluminum honeycomb buffer at different temperatures was studied. It is revealed that the aluminum honeycomb crushing force gradually decreases with the temperature increases. The peak pressure, burning rate coefficient and velocity increase while the peak time decreases with the temperature increase for the interior ballistics. For the launcher recoil responses, the average launch recoil decreases if the aluminum honeycomb doesn't enter the dense stage. The impact acceleration, projectile velocity and displacement increase as the temperature increase. The paper spotlights the temperature's influence on the recoil characteristics of the aluminum honeycomb buffer, which provides a new idea for buffering technology of pyrotechnic devices in a complex space environment.

Background and aim: Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway. Experimental procedure: The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN. Results and conclusion: The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.

The large size and complexity of most fern genomes have hampered efforts to elucidate fundamental aspects of fern biology and land plant evolution through genome-enabled research. Here we present a chromosomal genome assembly and associated methylome, transcriptome and metabolome analyses for the model fern species Ceratopteris richardii. The assembly reveals a history of remarkably dynamic genome evolution including rapid changes in genome content and structure following the most recent whole-genome duplication approximately 60 million years ago. These changes include massive gene loss, rampant tandem duplications and multiple horizontal gene transfers from bacteria, contributing to the diversification of defence-related gene families. The insertion of transposable elements into introns has led to the large size of the Ceratopteris genome and to exceptionally long genes relative to other plants. Gene family analyses indicate that genes directing seed development were co-opted from those controlling the development of fern sporangia, providing insights into seed plant evolution. Our findings and annotated genome assembly extend the utility of Ceratopteris as a model for investigating and teaching plant biology.

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis., Introduction Estimated new cases and deaths from renal cancer in the US for 2020 were 73,750 and 14,830 respectively (1). Kidney cancer incidence has been steadily increasing over the past [...]

Translocation renal cell carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed clear cell RCC driver) disrupted nephrogenesis and glomerular development, causing neonatal death, while the clear cell RCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as alveolar soft part sarcoma) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an epithelial-mesenchymal transition. Electron microscopy of tRCC tumors showed lysosome expansion, and functional studies revealed simultaneous activation of autophagy and mTORC1 pathways. Comparative genomic analyses encompassing an institutional human tRCC cohort (including a hitherto unreported SFPQ-TFEB fusion) and a variety of tumorgraft models (ASPSCR1-TFE3, PRCC-TFE3, SFPQ-TFE3, RBM10-TFE3, and MALAT1-TFEB) disclosed significant convergence in canonical pathways (cell cycle, lysosome, and mTORC1) and less established pathways such as Myc, E2F, and inflammation (IL-6/JAK/STAT3, interferon-[gamma], TLR signaling, systemic lupus, etc.). Therapeutic trials (adjusted for human drug exposures) showed antitumor activity of cabozantinib. Overall, this study provides insight into MiT/TFE-driven tumorigenesis, including the cell of origin, and characterizes diverse mouse models available for research., Introduction Renal cell carcinoma (RCC) is the most common malignant kidney epithelial neoplasm. Translocation renal cell carcinoma (tRCC) is an aggressive molecular subtype unusually prevalent in children and adolescents (1, [...]

Abstract Boundary dynamics are crucial for the transport of energy, mass, and momentum in geospace. The recently discovered plasmapause surface wave (PSW) plays a key role in the inner magnetosphere dynamics. However, a comprehensive investigation of spatial variations of the PSW remains absent. In this study, we elucidate the spatial characteristics of a PSW through observations from multiple spacecrafts in the magnetosphere. Following the initiation of the PSW, quasi‐periodic injections of energetic ions, rather than electrons, are suggested to serve as energy source of the PSW. Based on the distinct wave and particle signatures, we categorize the PSW into four regions: seed region, growth region, stabilization region and decay region, spanning from nightside to afternoon plasmapause. These findings advance our understanding of universal boundary dynamics and contribute to a deeper comprehension of the pivotal roles of surface waves in the energy couplings within the magnetosphere‐plasmasphere‐ionosphere system.

ObjectivesThis study aimed to analyze the influencing factors of hospitalization cost of hypertensive patients in TCM (traditional Chinese medicine, TCM) hospitals, which can provide a scientific basis for hospitals to control the hospitalization cost of hypertension.MethodsIn this study, 3,595 hospitalized patients with a primary diagnosis of tertiary hypertension in Tianshui City Hospital of TCM, Gansu Province, China, from January 2017 to June 2022, were used as research subjects. Using univariate analysis to identify the relevant variables of hospitalization cost, followed by incorporating the statistically significant variables of univariate analysis as independent variables in multiple linear regression analysis, and establishing the path model based on the results of the multiple linear regression finally, to explore the factors influencing hospitalization cost comprehensively.ResultsThe results showed that hospitalization cost of hypertension patients were mainly influenced by length of stay, age, admission pathways, payment methods of medical insurance, and visit times, with length of stay being the most critical factor.ConclusionThe Chinese government should actively exert the characteristics and advantages of TCM in the treatment of chronic diseases such as hypertension, consistently optimize the treatment plans of TCM, effectively reduce the length of stay and steadily improve the health literacy level of patients, to alleviate the illnesses pain and reduce the economic burden of patients.

Abstract Background and aims Liver regeneration retardation post partial hepatectomy (PH) is a common clinical problem after liver transplantation. Identification of key regulators in liver regeneration post PH may be beneficial for clinically improving the prognosis of patients after liver transplantation. This study aimed to clarify the function of junctional protein‐associated with coronary artery disease (JCAD) in liver regeneration post PH and to reveal the underlying mechanisms. Methods JCAD knockout (JCAD‐KO), liver‐specific JCAD‐KO (Jcad△Hep) mice and their control group were subjected to 70% PH. RNA sequencing was conducted to unravel the related signalling pathways. Primary hepatocytes from KO mice were treated with epidermal growth factor (EGF) to evaluate DNA replication. Fluorescent ubiquitination‐based cell cycle indicator (FUCCI) live‐imaging system was used to visualise the phases of cell cycle. Results Both global and liver‐specific JCAD deficiency postponed liver regeneration after PH as indicated by reduced gene expression of cell cycle transition and DNA replication. Prolonged retention in G1 phase and failure to transition over the cell cycle checkpoint in JCAD‐KO cell line was indicated by a FUCCI live‐imaging system as well as pharmacologic blockage. JCAD replenishment by adenovirus reversed the impaired DNA synthesis in JCAD‐KO primary hepatocyte in exposure to EGF, which was abrogated by a Yes‐associated protein (YAP) inhibitor, verteporfin. Mechanistically, JCAD competed with large tumour suppressor 2 (LATS2) for WWC1 interaction, leading to LATS2 inhibition and thereafter YAP activation, and enhanced expression of cell cycle‐associated genes. Conclusion JCAD deficiency led to delayed regeneration after PH as a result of blockage in cell cycle progression through the Hippo–YAP signalling pathway. These findings uncovered novel functions of JCAD and suggested a potential strategy for improving graft growth and function post liver transplantation. Key Points JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage. JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle‐associated genes. Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living‐donor liver transplantation.

High-tech protected cropping holds great potential to improve global food security, but high cooling energy costs in warm climates pose difficulties in propagating the industry. Emerging technologies, such as diffuse glasses fitted with photoselective thin films, have interactions with crops and other cooling technologies which are not well-characterized for warm-climate glasshouses. A light-blocking film (LBF) was chosen as a high-tech, climate-controlled greenhouse cover permitting transmission of 85% of photosynthetically-active light and blocking heat-generating radiation. Two consecutive 7-month trials of two capsicum crops were grown under warm climate conditions partially impacted by bushfire smoke, with 2 cultivars (Gina and O06614) in the first trial, and 2 cultivars (Gina and Kathia) in the second trial. Capsicum fruit yield decreased by 3% in Gina and increased by 3% in O06614 for the first trial, and decreased by 13% in Gina, 26% in Kathia for the second trial. Cooling energy use increased by 11% and 12% for both capsicum crops in AE and SE respectively, with small but insignificant decreases in fertigation demand (2%–5%). Cooling potential was significantly different from material specifications, with indications that convection from LBF interfaces was responsible for higher heat loads. LBF and similar absorptive glasses may still be beneficial for reducing nutrient, water, and energy use in warm climate glasshouses. However, yield is cultivar-dependent and may decrease with below-optimal crop lighting, whereas energy savings are more dependent on LBF orientation and building geometry than outside climate.

Background: With our growing insight into the molecular heterogeneity and biological characteristics of breast cancer, individualized treatment is the future of cancer treatment. In this prospective Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series study – neoadjuvant therapy (FASCINATE-N) trial, we classify breast cancer patients using multiomic characteristics into different subtypes to evaluate the efficacy of precision-based targeted therapies compared to standard neoadjuvant chemotherapy. Methods and design: The FASCINATE-N trial is a prospective, randomized, precision-based umbrella trial that plans to enroll 716 women with early breast cancer. After enrollment, patients will first be divided into three groups: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HER2+, and HR−/HER2−. The HR+/HER2− patients are further stratified using fusion and clustering of similarity network fusion (SNF) algorithm into four subtypes; HER2+ patients are divided into HR+/HER2+ and HR−/HER2+ subtypes; and HR−/HER2− patients are stratified using the Fudan University Shanghai Cancer Center classification. For the assignment of drugs to patients, Bayesian methods of adaptive randomization will be used. The primary endpoint is pathological complete response rate; secondary endpoints include 3-year invasive disease-free survival, overall response rate, and toxicities according to common terminology criteria for adverse events (CTCAE) scale version 4.0 and the ratio of patients with complete cell cycle arrest (Ki67 < 2.7%) in HR+/HER2+ breast cancer. Discussion: The goal of our trial is to test the efficacy of our subtyping-based treatment in a neoadjuvant setting and to conduct a pilot study into the efficacy of targeted therapies within each precision-based subtype. The precision-based treatment arm can be updated with the refinement of our subtyping method, the discovery of new targets, and the development of novel targeted drugs. Our trial offers a unique opportunity to provide patients with individualized neoadjuvant therapy and test promising novel treatments that may further benefit patients. Trial registration: ClinicalTrials.gov identifier: NCT05582499 ( https://classic.clinicaltrials.gov/ct2/show/NCT05582499 ).